Long non-coding RNA (lncRNA) H19 is associated with inflammatory diseases, but the molecular mechanism of H19 in the inflammatory process of ankylosing spondylitis (AS) is unclear. Here, we investigated the role of H19 and its downstream molecules in the inflammation of AS by microarray analysis, qRT-PCR, western blot, and dual-luciferase reporter assay. H19 small interfering RNA (siRNA) (Si-H19) and adenovirus (AD-H19) were used to decrease and increase H19 expression, respectively. 42 annotated lncRNAs were identified, and H19 was overexpressed. H19, vitamin D receptor (VDR), and transforming growth factor β (TGF-β) can bind to microRNA22-5p (miR22-5p) and miR675-5p. Si-H19 significantly downregulated miR22-5p and upregulated miR675-5p expression; Si-H19 decreased the protein and mRNA expression of VDR and decreased the cytokine and mRNA levels of interleukin-17A (IL-17A) and IL-23. These results were verified by AD-H19. In addition, miR22-5p and miR675-5p inhibitors increased the protein and mRNA expression of VDR and increased the cytokine and mRNA levels of IL-17A and IL-23. These results were also confirmed by miRNA mimics. Furthermore, H19 directly interfered with miR22-5p and miR675-5p expression, whereas the two miRNAs directly inhibited VDR expression. Overall, the H19-miR22-5p/miR675-5p-VDR-IL-17A/IL-23 signaling pathways have important roles in the pathogenesis of AS.
High
reactive oxygen species (ROS) generation efficiency and induction
of targeted cell apoptosis are recognized as key objectives to achieve
a highly efficient strategy for cancer therapy with minimum side effects
of inflammatory reactions. However, it is still a challenge to realize
higher therapeutic efficiency with a cell apoptosis model. Herein,
we present strong upconversion luminescent biosafe cores derived from
Linde Type A (LTA) zeolites and modification with targeted/therapeutic
drugs for multimodal therapy, in which sonodynamic therapy (SDT) combined
with photodynamic therapy (PDT) increases therapeutic efficiency especially
in deep sites of tumor via producing cytoplasmic ROS and mitochondrial
superoxide and photothermal therapy (PTT) enhances PDT effects via
higher fluorescence resonance energy transfer (FRET) efficacy attributed
to an increased temperature. Furthermore, the transcriptomic analysis
reveals that cellular internalization of the nanosystem can lead to
tumor ablation via cell apoptosis. We expect that the multimodal therapy
based on LTA zeolite drug nanocarriers could be applied in the cancer
therapeutics in the near future.
Carotid IMT was significantly increased in patients with AS compared with healthy controls, which suggested subclinical atherosclerosis is related to AS.
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